Obesity is pervasive and growing in industrialized societies. One important factor known to contribute to this increase is the availability of high-fat or high-calorie diets. Another factor to consider is individual predisposition to weight gain, due to genetic or early environmental influences. The goal of this research is to use innovative approaches to examine the role of brain peptides in relation to diet and predisposition. These neurochemicals are galanin (GAL) and neuropeptide Y (NPY), which in the hypothalamus are known to stimulate eating behavior and reduce energy expenditure but whose specific roles in obesity still remain to be elucidated. One main objective of this research is to determine whether, in models of dietary obesity that mimic the human condition, these peptides have a causal relationship to disturbances in eating and body weight control. Specifically, it is hypothesized that: a) GAL, in specific neurons of the paraventricular nucleus (PVN) that project to the median eminence (ME), contributes to increased body weight gain and adiposity in response to a high-fat diet; and b) NPY, in neurons of the arcuate nucleus (ARC) that project to the PVN, induces weight gain in response to a high-calorie diet with excess carbohydrate. This research program has been broadened to include new experimental models and techniques; simultaneous analyses of behavioral, endocrine, metabolic and neurochemical parameters; and studies of different animal populations. The proposed experiments will investigate, in: 1) Specific Aim 1, changes in neurobiological and metabolic systems induced by overeating of high-fat or high-carbohydrate diets in rats; 2) Specific Aim 2, the differential traits of obese and lean rats on high-fat or high-carbohydrate diets in rats; 3) Specific Aim 3, conditions in which chronic stimulation with GAL or NPY induces overeating and increases body fat; 4) Specific Aim 4, neuropeptide function in normal-weight rats with differential propensity toward obesity on a high-fat diet; 5) Specific Aim 5, effects of acute peptide injection on endocrine and metabolic systems that affect body fat accrual; 6) Specific Aim 6, the neuroendocrine and metabolic mechanisms underlying changes in peptides in response to fat-rich or carbohydrate-rich meals; 7) Specific Aim 7, neuropeptide traits in obesity-prone rats with higher insulin after a high-fat meal; and 8) Specific Aim 8, inbred mouse strains with different patterns of eating and weight gain. The overall objective of this research, in addition to defining the functional role of GAL and NPY, is to establish a program with different animal models, experimental strategies and multidisciplinary techniques that may broaden our perspective of brain function as it relates to energy balance.